BRD9 is an essential regulator of glycolysis that creates an epigenetic vulnerability in colon adenocarcinoma

Abstract Background The intensive interplay between aberrant epigenetic events and metabolic remodeling represents one of the hallmarks of tumors, including colon cancer. The functions of Bromodomain Containing Protein BRD‐9 in colon cancer remains indefinite. We aimed to identify the biological roles and clinical significance of BRD9 in colon cancer. Methods The univariate‐ and multi‐variate Cox regression models were used to screen risk epigenetic regulators. Kaplan–Meier analysis and Pearson correlation analysis were used to assess clinical significance of BRD9. CCK‐8 assays, colony formation assay, Transwell, and soft‐agar assay were performed to determine the in vitro roles of BRD9. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of colon cancer cells were evaluated by a Seahorse XF Extracellular Flux Analyzer. In vivo models and RT‐qPCR, western blotting, and Chromatin Immunoprecipitation (ChIP) assay were conducted to explore the functional roles of BRD9 in COAD. Results In the study, we detected the expressions of 662 epigenetic regulators in COAD and identified a series of 42 hazard epigenetic factors with p < 0.05. Low‐throughput MTT assays highlighted that BRD9 is an essential target, and targeting BRD9 could reduce significant decreases of cell growth. BRD9 overexpression could notably elevate proliferation and migration potentialities, whereas, BRD9 ablation abolished these effects. Mechanistically, functional enrichment analysis indicated the potential associations between BRD9 and glycolysis metabolism. In addition, BRD9 epigenetically coordinates the H3K27ac modifications on the promoter regions of ENO2 and ALDOC, inducing enhanced glycolysis activity. Lastly, I‐BRD9 could significantly suppress the growth of colon cancer cells in vitro and in vivo. Conclusions Together, our study revealed previously unidentified roles of BRD9 in colon cancer metabolism and tumor progression, indicating that BRD9 could be a valuable therapeutic target for COAD patients

Effect of detoxification methods on ABE production from corn stover hydrolysate by Clostridium acetobutylicum CICC 8016

In this study, effects of different single biomass derived inhibitors on acetone–butanol–ethanol (ABE) production by Clostridium acetobutylicum CICC 8016 were first investigated. The results showed that formic acid, coumaric acid, and furfural at 0.5 g/L (sodium formate equivalent) inhibited ABE production. Furthermore, corn stover hydrolysate media were prepared following dilute acid pretreatment, enzymatic hydrolysis, and detoxification with different methods. Among overliming, steam stripping, acetone–ethyl ether extraction, and ion exchange with five anion resins, adsorption with resin D301 showed the highest efficiency for inhibitor removal (99–100% of phenolics and 87–99% of sugar degradation products). Without detoxification, ABE production was lower than 1.0 g/L from 28.1 g/L sugars whereas ABE production with medium detoxified by D301 resin achieved higher ABE concentrations and yields than control with synthetic medium. Correlation analysis further revealed that formic acid, coumaric acid, and total phenolics were the major compounds inhibiting ABE production. The results also showed that the single detoxification method was sufficient to detoxify the hydrolysate for ABE production at the pretreatment conditions used in this study.</p

A study on Clostridium spp. exposure level on infant population in some parts of China

Objective A case-control study on Clostridium spp. contamination on infant population and infant formula powdered was carried out, the data on Clostridium spp. exposure in some parts of China was obtained. Methods Epidemiological information and samples were collected from 6 locations in 6 provinces in China. The isolation and identification, of Clostridium spp. were performed. Results Totally 501 infants were investigated. Among them, 247 were exclusive breastfeeding and 254 were mixed feeding. According to the month grouping, 367 were 0-6 months and 134 were 7-12 months. A total of 813 samples were collected. After testing, 246 strains of Clostridium spp. were obtained and the positive rate was 30.3% (246/813). C. sporogenes (8.4%, 68/813), C. bifermentans (6.2%, 50/813) and C. butyricum (4.6%, 37/813) had the highest detection rate.37.3% (187/501) of the stool samples were Clostridium spp. positive, followed by 22.3% (27/121) of the infant formula powder, 19.5% (25/128) of the environmental swab and 11.1% (7/63) of the food samples. The detection rate of Clostridium spp. in mixed feeding group was significantly higher than that of breast-feeding group (χ2=40.833, P<0.01), and 7-12-month-old group was significantly higher than that of 0-6 months group (χ2=27.829, P<0.01). Conclusion There was a high exposure level of Clostridium spp. in food and environment in infant population in some parts of China

A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother’s own milk for preterm infants in the NICU

Abstract Background Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks’ gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother’s own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed. Methods Our prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks’ gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors. Discussion Our double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants. Trial registration Chinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019; http://www.chictr.org.cn/showprojen.aspx?proj=3427